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Updated: Jun 27, 2026

Retinal Pathophysiological Evaluation in a Rat Model
Published on: May 6, 2022
Diabetes reduces autophosphorylation of retinal insulin receptor and increases protein-tyrosine phosphatase-1B
Raju V S Rajala1, Brandt Wiskur, Masaki Tanito
1Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. raju-rajala@ouhsc.edu
Purpose:
Protein-tyrosine phosphatase-1B (PTP1B) has been implicated in the negative regulation of insulin signaling. The expression, activity, and functional role of PTP1B in the retina are unknown. In this study, the authors examined the relationship between the retinal insulin receptor (IR) and PTP1B in normal and diabetic mouse retinas.
Methods:
IR and PTP1B localization was examined by immunohistochemistry. The activation of IR was analyzed using specific antibodies against phosphotyrosine. PTP1B activity was determined in anti-PTP1B immunoprecipitates. Glutathione-S-transferase fusion proteins containing wild-type and catalytically inactive mutant PTP1B was used to study the interaction between IR and PTP1B. Anti-IR immunoprecipitates and the cytoplasmic domain of purified IR were incubated in the presence of ATP, and the autophosphorylation of IR with antiphosphotyrosine antibody was analyzed.
Results:
Immunohistochemical analysis of PTP1B shows that it is predominantly expressed in nonphotoreceptor layers of the retina, though it is clearly expressed in the inner segments of the rod photoreceptors. The IR is predominately expressed in rod inner segments. Biochemical analysis of rod outer segments indicates the presence of IR and PTP1B. Retinal IR exhibits a high level of basal autophosphorylation, and this autophosphorylation is reduced in diabetic mouse retinas. In vitro, PTP1B is able to dephosphorylate the autophosphorylated IR. Substrate mutant-trap results indicate a stable interaction between IR and PTP1B. Further, PTP1B activity was increased in diabetic mouse retinas.
Conclusions:
These studies indicate that diabetes reduces the autophosphorylation of retinal IR and increased PTP1B activity. Further, PTP1B regulates the state of IR phosphorylation in the retina.
Insights
Diabetes reduces retinal insulin receptor (IR) autophosphorylation by increasing protein-tyrosine phosphatase-1B (PTP1B) activity. PTP1B regulates IR phosphorylation in the retina.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- Protein-tyrosine phosphatase-1B (PTP1B) is known to negatively regulate insulin signaling.
- The role and expression of PTP1B in the retina remain largely uncharacterized.
- Understanding PTP1B's function in the retina is crucial for comprehending diabetic retinopathy.
Purpose of the Study:
- To investigate the expression, activity, and functional role of PTP1B in the retina.
- To examine the relationship between the retinal insulin receptor (IR) and PTP1B in normal and diabetic mouse models.
- To determine how diabetes affects PTP1B and IR interaction and phosphorylation in the retina.
Main Methods:
- Immunohistochemistry was used to localize IR and PTP1B expression in retinal tissues.
- IR activation was assessed via antibodies targeting phosphotyrosine.
- PTP1B activity was measured in immunoprecipitates, and its interaction with IR was studied using glutathione-S-transferase fusion proteins.
Main Results:
- PTP1B is expressed in nonphotoreceptor layers and rod photoreceptor inner segments; IR is predominantly in rod inner segments.
- Diabetic mouse retinas showed reduced IR autophosphorylation and increased PTP1B activity.
- In vitro studies confirmed PTP1B dephosphorylates and interacts with the autophosphorylated IR.
Conclusions:
- Diabetes mellitus leads to decreased retinal IR autophosphorylation and elevated PTP1B activity.
- PTP1B plays a significant role in regulating the phosphorylation status of the retinal IR.
- These findings highlight PTP1B as a potential therapeutic target for diabetic eye complications.
Related Concept Videos
Insulin: The Receptor and Signaling Pathways
Diabetic Retinopathy
Type I Diabetes I: Introduction
Type I Diabetes II: Pathophysiology
Type II Diabetes II: Pathophysiology
Type II Diabetes I: Introduction

